Figure 8

Examples of convergent binding sites on apparently unrelated enzymes, tightly superimposed by APF method: (a) GDP bound to gdp-mannose mannosyl hydrolase (1rya, magenta) and to calcium-dependent endoplasmic reticulum nucleoside diphosphatase (1s1d, green). Residues coordinating guanidyl moiety – the sidechains of K161, W163, Y237 and the backbone of T164 in 1rya align well in space and play the role of R52, F3, and F9 and the backbone of L4 in 1s1d. 1rya belongs to NUDIX hydrolase superfamily and alpha and beta fold class, while 1s1d is classified as apyrase and 5-bladed beta-propeller, according to CDD[27] and SCOP[28]. (b) Binding sites of concanavalin A (1cjp, magenta) and agglutinin (1jot, green). Despite lack of any overall homology, the two proteins bind the central sugar moieties (glucose in concanavalin A complex and galactose in agglutinin complex) of their ligands in a remarkably similar manner: beta-hairpins G98-L99-Y100 (concanavalin A) and G121-Y122-W123 (agglutinin) coordinate O5’ and O6 atoms via backbone hydrogen bonds; Y12 (concavalin A) and Y78 (agglutinin) engage aliphatic carbons on the opposite face of the sugar ring in hydrophobic interactions; D208 and D125 coordinate hydrogens on O4 and O6 hydroxyl oxygens. Parts of ligands other than the central sugar moiety are shown in wire representation for clarity.